Metabolic Dysfunction-associated Liver DiseaseESTEATOVEGNCT07503431
Effect of Plant-based Diets on Liver Biomarkers, Cardiometabolic Health, and Exposure to Environmental Contaminants and Endocrine Disruptors in Patients With Metabolic Liver Disease.
A study testing Traditional Mediterranean diet and Vegan Mediterranean diet in people with Metabolic Dysfunction-associated Liver Disease, run by Miguel López Moreno at 1 site in Spain.
Trial summary
Plant-based diets have gained increasing recognition for their sustainability and their benefits on cardiometabolic and liver health. However, evidence regarding their effects in patients with metabolic liver disease (MetLD) remains limited. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Metabolic Dysfunction-associated Liver Disease
- What is being tested?
- Traditional Mediterranean diet and Vegan Mediterranean diet
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteSpain
- Study dates
- 18 Apr 2026to 10 Mar 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults aged 18 to 75 years.
- Diagnosis of metabolic dysfunction-associated liver disease (MetLD) based on evidence of hepatic steatosis by ultrasound or transient elastography with controlled attenuation parameter (CAP) ≥ 275 dB/m, or liver biopsy.
- Body mass index (BMI) between 25 and 38.5 kg/m².
Who cannot join
- Liver disease of etiology other than MetLD.
- Any condition requiring specific dietary treatment and/or limiting adherence to a plant-based diet.
- Acute or chronic diseases that may reduce life expectancy.
- Type 1 diabetes mellitus.
- Use of weight-loss medications (e.g., incretin-based therapies) or initiation of glucose-lowering medication within the past 6 months.
- Pregnancy or breastfeeding.
Show all 9Show fewer
- Pharmacological treatments that may interfere with study outcomes (e.g., corticosteroids or biological therapies).
- Uncontrolled psychiatric disorders.
- Inability to provide informed consent.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Spain1 site
Hospital Puerta del Hierro
Madrid
Jesús Rivera, 636874519, jesusriveraest@gmail.com
About this study
Plant-based diets have gained increasing recognition for their sustainability and their benefits on cardiometabolic and liver health. However, evidence regarding their effects in patients with metabolic liver disease (MetLD) remains limited. The primary objective of this project is to compare the effects of a traditional Mediterranean diet and a Mediterranean diet exclusively based on plant-derived foods on liver parameters, cardiometabolic health, gut microbiota, and exposure to environmental contaminants in patients with MetLD.
This study is a randomized clinical trial with a 1:1 allocation ratio into two groups: a traditional Mediterranean diet, considered the standard diet in our setting and recommended for this condition, and a Mediterranean diet exclusively based on plant-derived foods, both designed by registered dietitians. The intervention will last 12 weeks.
Read more
Anthropometric, metabolic, hepatic, inflammatory, and quality of life variables will be assessed. Additionally, gut microbiota, genetic variants associated with MetLD, and internal exposure to environmental contaminants will be evaluated using biological samples. A 4-week follow-up after the intervention will also be conducted to assess the integration of lifestyle recommendations among participants.
The results will contribute to the development of safe, sustainable, and cost-effective nutritional strategies and may serve as a basis for future clinical guidelines integrating precision nutrition and planetary health in the management of chronic liver diseases.
The traditional Mediterranean diet has shown metabolic and hepatic benefits; however, its reformulation toward a predominantly plant-based pattern may enhance these effects by reducing saturated fat intake and increasing the consumption of fiber, bioactive compounds, and fatty acids with a more favorable profile. Moreover, this type of diet limits the intake of animal-based foods associated with the bioaccumulation of environmental contaminants such as PFAS and heavy metals, which are increasingly implicated in the progression of MetLD.
This project hypothesizes that a Mediterranean diet based exclusively on plant-derived foods, compared to a traditional Mediterranean diet, will lead to greater improvements in hepatic, metabolic, and inflammatory parameters in patients with MetLD, and will additionally be associated with a lower internal burden of bioaccumulative environmental contaminants.
Primary objective To evaluate the effect of a Mediterranean diet based exclusively on plant-derived foods on MetLD, assessed non-invasively through biochemical and elastographic parameters.
Secondary objectives To evaluate changes in metabolic parameters, anthropometric measures, and body composition.
To examine changes in systemic inflammatory markers, such as C-reactive protein and the neutrophil-to-lymphocyte ratio.
To assess exposure to environmental contaminants, specifically heavy metals (lead, cadmium, mercury) and endocrine disruptors such as perfluorinated compounds (PFAS), and their relationship with liver damage.
To evaluate whether genetic variants associated with susceptibility to and progression of MetLD modulate hepatic and metabolic responses to dietary patterns.
To analyze changes in gut microbiota following the plant-based diet and their association with liver improvement.
Read the detailed description
Metabolic dysfunction-associated liver disease (MetLD) is currently the most prevalent chronic liver disease worldwide, representing the hepatic manifestation of metabolic syndrome and closely associated with obesity, type 2 diabetes mellitus, dyslipidemia, and hypertension. Its global burden continues to rise in parallel with increasing rates of cardiometabolic disorders, posing a major public health challenge. The natural history of MetLD ranges from simple steatosis to steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Disease progression is influenced by a complex interplay of metabolic, genetic, environmental, and lifestyle-related factors.
Lifestyle modification remains the cornerstone of MetLD management, with dietary intervention being a key therapeutic strategy. Current clinical guidelines recommend the Mediterranean diet as the standard dietary approach, given its demonstrated benefits in reducing hepatic steatosis, improving insulin sensitivity, lowering systemic inflammation, and enhancing overall cardiometabolic health. Notably, these benefits have been observed even in the absence of substantial weight loss.
In recent years, plant-based dietary patterns have gained increasing attention due to their potential to further improve metabolic and hepatic outcomes. Diets rich in plant-derived foods are characterized by higher intakes of dietary fiber, polyphenols, antioxidants, and unsaturated fatty acids, alongside lower intakes of saturated fats and cholesterol. These nutritional characteristics may contribute to improved insulin sensitivity, modulation of lipid metabolism, and attenuation of chronic low-grade inflammation.
Furthermore, plant-based diets may influence liver health through mechanisms beyond traditional metabolic pathways. Emerging evidence highlights the role of environmental contaminants and endocrine-disrupting chemicals in the pathogenesis and progression of MetLD. Compounds such as per- and polyfluoroalkyl substances (PFAS) and heavy metals (e.g., cadmium, lead, mercury) have been associated with oxidative stress, mitochondrial dysfunction, alterations in glucose and lipid homeostasis, and hepatic injury. These contaminants are known to bioaccumulate predominantly in animal-derived foods, including fish, seafood, red meat, and organ meats. Therefore, dietary patterns that reduce or eliminate animal-based foods may lower internal exposure to these harmful substances.
In addition to environmental exposures, genetic susceptibility and gut microbiota composition play critical roles in MetLD development and progression. Genetic variants such as PNPLA3, TM6SF2, MBOAT7, GCKR, and HSD17B13 have been consistently associated with liver fat accumulation, inflammation, and fibrosis. Meanwhile, the gut microbiota acts as a key regulator of host metabolism and immune function through the gut-liver axis, influencing bile acid metabolism, short-chain fatty acid production, and inflammatory signaling pathways. Diet is one of the main determinants of microbiota composition and function, and plant-based diets have been associated with increased microbial diversity and beneficial metabolic profiles.
Despite these advances, there is currently a lack of randomized clinical trials specifically evaluating the effects of a Mediterranean diet exclusively based on plant-derived foods in patients with MetLD, particularly considering the integrated assessment of hepatic outcomes, cardiometabolic risk factors, gut microbiota, genetic susceptibility, and environmental contaminant exposure.
This study is a randomized, controlled, parallel-group clinical trial designed to compare the effects of two dietary interventions: (1) a traditional Mediterranean diet, which includes both plant- and animal-based foods and is considered the standard of care in this setting, and (2) a Mediterranean diet exclusively based on plant-derived foods. Participants will be randomly allocated in a 1:1 ratio using a computer-generated randomization sequence with stratification by age and sex.
The intervention will last 12 weeks, followed by a 4-week post-intervention follow-up period aimed at evaluating adherence, sustainability, and integration of lifestyle changes. The study adopts a pragmatic design to enhance external validity, allowing participants to follow ad libitum dietary intake within structured dietary guidelines, guided by internal hunger and satiety cues rather than strict caloric prescriptions.
All participants will undergo a comprehensive baseline assessment, including clinical evaluation, dietary assessment, anthropometric measurements, blood pressure, and non-invasive liver evaluation using transient elastography with controlled attenuation parameter (CAP). Biological samples (blood, urine, feces, and hair) will be collected at baseline and at the end of the intervention to allow intra-individual comparisons.
Dietary interventions will be individually tailored by registered dietitians based on participants' clinical characteristics, preferences, and estimated energy requirements. Both dietary patterns will emphasize whole, minimally processed foods and adherence to Mediterranean dietary principles. The plant-based intervention group will exclude all animal-derived foods and will receive standardized vitamin B12 supplementation to prevent deficiencies.
Dietary intake will be monitored through repeated 24-hour dietary recalls conducted at multiple time points throughout the intervention, including both weekdays and weekends. Participants will also provide photographic records of meals to enhance data accuracy. Nutrient intake will be analyzed using specialized dietary analysis software. Continuous dietary counseling and support will be provided to promote adherence.
Comprehensive outcome assessments will include biochemical, metabolic, inflammatory, and functional parameters. Laboratory analyses will include liver enzymes, lipid profile, glucose metabolism markers, iron status, and systemic inflammatory markers such as C-reactive protein and the neutrophil-to-lymphocyte ratio.
Environmental exposure assessment will include quantification of PFAS in serum samples using high-performance liquid chromatography coupled with tandem mass spectrometry and isotopic dilution techniques. Heavy metals will be measured in hair samples using inductively coupled plasma mass spectrometry (ICP-MS/MS), providing an estimate of chronic exposure.
Gut microbiota composition will be analyzed using 16S rRNA gene sequencing, focusing on diversity indices, taxonomic composition, and functional profiles. Genetic analyses will be performed on blood samples to identify polymorphisms associated with MetLD susceptibility and progression.
Standardized and validated questionnaires will be used to assess physical activity, adherence to the Mediterranean diet, and quality of life. Additionally, body composition will be evaluated using bioelectrical impedance analysis, and muscle strength will be assessed using handgrip dynamometry.
The primary objective of the study is to evaluate the effect of a plant-based Mediterranean diet on liver health, assessed non-invasively through elastographic and biochemical parameters. Secondary objectives include the evaluation of changes in anthropometric and cardiometabolic parameters, systemic inflammation, gut microbiota composition, genetic modulation of dietary response, and internal exposure to environmental contaminants.
Data will be collected and managed using a secure electronic data capture system, ensuring data quality, confidentiality, and compliance with regulatory standards. Statistical analyses will be performed using appropriate descriptive and inferential methods, including multivariate regression models to account for potential confounders.
The study will be conducted in accordance with the principles of Good Clinical Practice and the Declaration of Helsinki. Ethical approval will be obtained from the relevant institutional review board, and all participants will provide written informed consent prior to inclusion.
This study is expected to provide novel, integrative evidence on the role of dietary patterns in modulating liver health, metabolic function, environmental exposures, and host-microbiome interactions. The findings may contribute to the development of more effective, sustainable, and personalized nutritional strategies for the prevention and management of MetLD, supporting the integration of precision nutrition and planetary health into clinical practice.
- Being tested
- Traditional Mediterranean diet, Vegan Mediterranean diet
- Keywords
- Metabolic dysfunction-associated liver disease, plant-based diet, mediterranean diet
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Traditional Mediterranean dietOther
This dietary pattern is considered the standard of care in the study setting and includes a balanced intake of plant- and animal-derived foods, consistent with current clinical recommendations for metabolic liver disease.
The diet emphasizes high consumption of vegetables, fruits, legumes, whole grains, nuts, seeds, and olive oil as the primary source of fat. Moderate intake of fish, poultry, eggs, and low-fat dairy products will be encouraged, while red and processed meats, added sugars, and ultra-processed foods will be limited.
Vegan Mediterranean dietOther
This dietary pattern is designed and supervised by registered dietitians and emphasizes high consumption of vegetables, fruits, legumes, whole grains, nuts, seeds, and olive oil as the primary source of fat, in line with Mediterranean dietary principles.
All animal-derived foods (including meat, fish, seafood, dairy products, and eggs) will be excluded. Legumes, whole grains, nuts, and seeds will serve as the main sources of protein and healthy fats. Participants will be encouraged to prioritize whole, minimally processed foods; however, plant-based alternatives to meat and dairy may be allowed in cases where necessary to support adherence.
| Study group | Role | What they receive |
|---|---|---|
| Traditional Mediterranean diet | Experimental | This dietary pattern is considered the standard of care in the study setting and includes a balanced intake of plant- and animal-derived foods, consistent with current clinical recommendations for metabolic liver disease.
The diet emphasizes high consumption of vegetables, fruits, legumes, whole grains, nuts, seeds, and olive oil as the primary source of fat. Moderate intake of fish, poultry, eggs, and low-fat dairy products will be encouraged, while red and processed meats, added sugars, and ultra-processed foods will be limited. Receives: Other: Traditional Mediterranean diet |
| Vegan Mediterranean diet | Experimental | This dietary pattern is designed and supervised by registered dietitians and emphasizes high consumption of vegetables, fruits, legumes, whole grains, nuts, seeds, and olive oil as the primary source of fat, in line with Mediterranean dietary principles.
All animal-derived foods (including meat, fish, seafood, dairy products, and eggs) will be excluded. Legumes, whole grains, nuts, and seeds will serve as the main sources of protein and healthy fats. Participants will be encouraged to prioritize whole, minimally processed foods; however, plant-based alternatives to meat and dairy may be allowed in cases where necessary to support adherence. Receives: Other: Vegan Mediterranean diet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Body weight
Change from baseline to 12 weeks in body weight (kg), measured using bioelectrical impedance analysis under standardized conditions.
Measured: Baseline and 12 weeks
Hepatic steatosis
Change from baseline to 12 weeks in hepatic steatosis measured non-invasively using transient elastography. Hepatic steatosis will be assessed by the controlled attenuation parameter (CAP, dB/m)
Measured: Baseline and 12 weeks
Secondary outcomes (23)
Liver stiffness
Change from baseline to 12 weeks in liver stiffness, measured non-invasively using transient elastography. Liver stiffness will be expressed in kilopascals (kPa).
Measured: Baseline and 12 weeks
Fat mass
Change from baseline to 12 weeks in total fat mass measured by bioelectrical impedance analysis (BIA) under standardized conditions.
Measured: Baseline and 12 weeks
Waist circumference
Change from baseline to 12 weeks in waist circumference as a marker of central adiposity.
Measured: Baseline and 12 weeks
Systolic blood pressure
Change from baseline to 12 weeks in systolic blood pressure (mmHg) measured using a validated device under standardized conditions.
Measured: Baseline and 12 weeks
Diastolic blood pressure
Change from baseline to 12 weeks in diastolic blood pressure (mmHg) measured under standardized conditions.
Measured: Baseline and 12 weeks
Fasting glucose
Change from baseline to 12 weeks in fasting plasma glucose (mg/dL) measured using standard laboratory methods.
Measured: Baseline and 12 weeks
Fasting insulin
Change from baseline to 12 weeks in fasting insulin levels (µIU/mL) measured in blood samples.
Measured: Baseline and 12 weeks
Total cholesterol
Change from baseline to 12 weeks in total cholesterol levels (mg/dL) measured using standard laboratory assays.
Measured: Baseline and 12 weeks
Low-density lipoprotein cholesterol
Change from baseline to 12 weeks in low-density lipoprotein cholesterol (mg/dL)
Measured: Baseline and 12 weeks
High-density lipoprotein cholesterol
Change from baseline to 12 weeks in high-density lipoprotein cholesterol (mg/dL)
Measured: Baseline and 12 weeks
Triglycerides
Change from baseline to 12 weeks in triglyceride levels (mg/dL)
Measured: Baseline and 12 weeks
Iron status
Change from baseline to 12 weeks in serum iron measured in blood samples.
Measured: Baseline and 12 weeks
Ferritin
Change from baseline to 12 weeks in ferritin measured in blood samples.
Measured: Baseline and 12 weeks
Transferrin saturation
Change from baseline to 12 weeks in transferrin saturation measured in blood samples.
Measured: Baseline and 12 weeks
C-reactive protein
Change from baseline to 12 weeks in serum C-reactive protein as a marker of systemic inflammation.
Measured: Baseline and 12 weeks
Neutrophil-to-lymphocyte ratio
Change from baseline to 12 weeks in the neutrophil-to-lymphocyte ratio calculated from complete blood count.
Measured: Baseline and 12 weeks
Gut microbiota alpha diversity
Change from baseline to 12 weeks in gut microbiota beta diversity reflecting differences in microbial composition between samples.
Measured: Baseline and 12 weeks
Gut microbiota taxonomic composition
Change from baseline to 12 weeks in relative abundance of bacterial taxa assessed by 16S rRNA sequencing.
Measured: Baseline and 12 weeks
Serum PFAS concentrations
Change from baseline to 12 weeks in serum levels of per- and polyfluoroalkyl substances (PFAS), measured by HPLC-MS/MS.
Measured: Baseline and 12 weeks
Change in hair heavy metal concentrations (lead, cadmium, mercury, arsenic)
Change from baseline to 12 weeks in heavy metal concentrations measured in hair samples using ICP-MS/MS.
Measured: Baseline and 12 weeks
Genetic variants
Assessment of genetic polymorphisms (e.g., PNPLA3, TM6SF2, MBOAT7, GCKR, HSD17B13) and their association with response to dietary intervention.
Measured: Baseline
Health-related quality of life
Change from baseline to 12 weeks in general quality of life assessed using the 36-Item Short Form Health Survey (SF-36) questionnaire. The SF-36 is a validated instrument that evaluates health-related quality of life across multiple domains, with scores ranging from 0 to 100, where higher scores indicate better perceived health status and quality of life.
Measured: Baseline and 12 weeks
Liver disease-specific quality of life
Change from baseline to 12 weeks in disease-specific quality of life assessed using the Chronic Liver Disease Questionnaire (CLDQ). The CLDQ is a validated instrument designed to assess quality of life in individuals with chronic liver disease, with scores ranging from 1 to 7, where higher scores indicate better quality of life and fewer symptoms.
Measured: Baseline and 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Mar 2026
- Study start18 Apr 2026 (estimated)
- Primary completion19 Dec 2026 (estimated)
- Study completion10 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Metabolic Dysfunction-associated Liver DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Care provider, Outcomes assessor
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Miguel López Moreno
- Sponsor type
- University, hospital or other
- Collaborators
- IMDEA Food, Hospital Clinico Universitario San Cecilio, Puerta de Hierro University Hospital
- Responsible party
- Sponsor-investigator, Miguel López Moreno, Universidad Francisco de Vitoria
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07503431
- Sponsor's protocol ID
- PI 22/26
- Acronym
- ESTEATOVEG
- Status last verified
- Mar 2026
- First submitted
- 25 Mar 2026
- Last updated
- 6 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data (IPD) will not be shared.
Publications
Younossi ZM, Zelber-Sagi S, Lazarus JV, Wong VW, Yilmaz Y, Duseja A, Eguchi Y, Castera L, Pessoa MG, Oliveira CP, El-Kassas M, Tsochatzis E, Fan JG, Spearman CW, Tacke F, Castellanos Fernandez MI, Alkhouri N, Schattenberg JM, Romero-Gomez M, Noureddin M, Allen AM, Ong JP, Roberts SK, Shubrook JH, Burra P, Kohli R, Kautz A, Holleboom AG, Lam B, Isaacs S, Macedo P, Gastaldelli A, Henry L, Ivancovsky-Wajcman D, Nader F, de Avila L, Price JK, Mark HE, Villota-Rivas M, Barbera A, Kalligeros M, Gerber LH, Alqahtani SA. Global Consensus Recommendations for Metabolic Dysfunction-Associated Steatotic Liver Disease and Steatohepatitis. Gastroenterology. 2025 Oct;169(5):1017-1032.e2. doi: 10.1053/j.gastro.2025.02.044. Epub 2025 Apr 11.
PubMed 40222485European Association for the Study of the Liver (EASL); European Association for the Study of Diabetes (EASD); European Association for the Study of Obesity (EASO). EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). J Hepatol. 2024 Sep;81(3):492-542. doi: 10.1016/j.jhep.2024.04.031. Epub 2024 Jun 7.
PubMed 38851997Lopez-Moreno M, Kraselnik A. The Impact of Plant-Based Proteins on Muscle Mass and Strength Performance: A Comprehensive Review. Curr Nutr Rep. 2025 Feb 21;14(1):37. doi: 10.1007/s13668-025-00628-1.
PubMed 39982647Lopez-Moreno M, Fresan U. Do the Health Benefits of the Mediterranean Diet Increase with a Higher Proportion of Whole Plant-Based Foods? Curr Nutr Rep. 2025 Mar 26;14(1):52. doi: 10.1007/s13668-025-00647-y.
PubMed 40138066Lopez-Moreno M, Marrero-Fernandez P, Galiana C, Aguilar-Navarro M, Munoz A, Gutierrez-Hellin J, Fresan U. Environmental and economic impact of a vegan versus traditional mediterranean diet: OMNIVEG study. Eur J Nutr. 2026 Mar 17;65(3):97. doi: 10.1007/s00394-026-03939-3.
PubMed 41843153Lopez-Moreno M, Fresan U, Del Coso J, Aguilar-Navarro M, Iglesias Lopez MT, Pena-Fernandez J, Munoz A, Gutierrez-Hellin J. The OMNIVEG STUDY: Health outcomes of shifting from a traditional to a vegan Mediterranean diet in healthy men. A controlled crossover trial. Nutr Metab Cardiovasc Dis. 2024 Dec;34(12):2680-2689. doi: 10.1016/j.numecd.2024.08.008. Epub 2024 Aug 23.
PubMed 39358106
Study at a glance
From the registry record, last updated by the sponsor on 6 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Plant-based Diets on Liver Biomarkers, Cardiometabolic Health, and Exposure to Environmental Contaminants and Endocrine Disruptors in Patients With Metabolic Liver Disease.
- ClinicalTrials.gov ID
- NCT07503431
- Acronym / sponsor ID
- ESTEATOVEG / PI 22/26
- Keywords
- Metabolic dysfunction-associated liver disease, plant-based diet, mediterranean diet
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Miguel López MorenoUniversity, hospital or other
- Collaborators
- IMDEA Food, Hospital Clinico Universitario San Cecilio, Puerta de Hierro University Hospital
- Study start
- 18 Apr 2026 (estimated)
- Primary completion
- 19 Dec 2026 (estimated)
- Study completion
- 10 Mar 2027 (estimated)
- First posted
- 31 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Plant-based diets have gained increasing recognition for their sustainability and their benefits on cardiometabolic and liver health. However, evidence regarding their effects in patients with metabolic liver disease (MetLD) remains limited. The primary objective of this project is to compare the effects of a traditional Mediterranean diet and a Mediterranean diet exclusively based on plant-derived foods on liver parameters, cardiometabolic health, gut microbiota, and exposure to environmental contaminants in patients with MetLD.
This study is a randomized clinical trial with a 1:1 allocation ratio into two groups: a traditional Mediterranean diet, considered the standard diet in our setting and recommended for this condition, and a Mediterranean diet exclusively based on plant-derived foods, both designed by registered dietitians. The intervention will last 12 weeks.
Anthropometric, metabolic, hepatic, inflammatory, and quality of life variables will be assessed. Additionally, gut microbiota, genetic variants associated with MetLD, and internal exposure to environmental contaminants will be evaluated using biological samples. A 4-week follow-up after the intervention will also be conducted to assess the integration of lifestyle recommendations among participants.
The results will contribute to the development of safe, sustainable, and cost-effective nutritional strategies and may serve as a basis for future clinical guidelines integrating precision nutrition and planetary health in the management of chronic liver diseases.
The traditional Mediterranean diet has shown metabolic and hepatic benefits; however, its reformulation toward a predominantly plant-based pattern may enhance these effects by reducing saturated fat intake and increasing the consumption of fiber, bioactive compounds, and fatty acids with a more favorable profile. Moreover, this type of diet limits the intake of animal-based foods associated with the bioaccumulation of environmental contaminants such as PFAS and heavy metals, which are increasingly implicated in the progression of MetLD.
This project hypothesizes that a Mediterranean diet based exclusively on plant-derived foods, compared to a traditional Mediterranean diet, will lead to greater improvements in hepatic, metabolic, and inflammatory parameters in patients with MetLD, and will additionally be associated with a lower internal burden of bioaccumulative environmental contaminants.
Primary objective To evaluate the effect of a Mediterranean diet based exclusively on plant-derived foods on MetLD, assessed non-invasively through biochemical and elastographic parameters.
Secondary objectives To evaluate changes in metabolic parameters, anthropometric measures, and body composition.
To examine changes in systemic inflammatory markers, such as C-reactive protein and the neutrophil-to-lymphocyte ratio.
To assess exposure to environmental contaminants, specifically heavy metals (lead, cadmium, mercury) and endocrine disruptors such as perfluorinated compounds (PFAS), and their relationship with liver damage.
To evaluate whether genetic variants associated with susceptibility to and progression of MetLD modulate hepatic and metabolic responses to dietary patterns.
To analyze changes in gut microbiota following the plant-based diet and their association with liver improvement.
Detailed description
Metabolic dysfunction-associated liver disease (MetLD) is currently the most prevalent chronic liver disease worldwide, representing the hepatic manifestation of metabolic syndrome and closely associated with obesity, type 2 diabetes mellitus, dyslipidemia, and hypertension. Its global burden continues to rise in parallel with increasing rates of cardiometabolic disorders, posing a major public health challenge. The natural history of MetLD ranges from simple steatosis to steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Disease progression is influenced by a complex interplay of metabolic, genetic, environmental, and lifestyle-related factors.
Lifestyle modification remains the cornerstone of MetLD management, with dietary intervention being a key therapeutic strategy. Current clinical guidelines recommend the Mediterranean diet as the standard dietary approach, given its demonstrated benefits in reducing hepatic steatosis, improving insulin sensitivity, lowering systemic inflammation, and enhancing overall cardiometabolic health. Notably, these benefits have been observed even in the absence of substantial weight loss.
In recent years, plant-based dietary patterns have gained increasing attention due to their potential to further improve metabolic and hepatic outcomes. Diets rich in plant-derived foods are characterized by higher intakes of dietary fiber, polyphenols, antioxidants, and unsaturated fatty acids, alongside lower intakes of saturated fats and cholesterol. These nutritional characteristics may contribute to improved insulin sensitivity, modulation of lipid metabolism, and attenuation of chronic low-grade inflammation.
Furthermore, plant-based diets may influence liver health through mechanisms beyond traditional metabolic pathways. Emerging evidence highlights the role of environmental contaminants and endocrine-disrupting chemicals in the pathogenesis and progression of MetLD. Compounds such as per- and polyfluoroalkyl substances (PFAS) and heavy metals (e.g., cadmium, lead, mercury) have been associated with oxidative stress, mitochondrial dysfunction, alterations in glucose and lipid homeostasis, and hepatic injury. These contaminants are known to bioaccumulate predominantly in animal-derived foods, including fish, seafood, red meat, and organ meats. Therefore, dietary patterns that reduce or eliminate animal-based foods may lower internal exposure to these harmful substances.
In addition to environmental exposures, genetic susceptibility and gut microbiota composition play critical roles in MetLD development and progression. Genetic variants such as PNPLA3, TM6SF2, MBOAT7, GCKR, and HSD17B13 have been consistently associated with liver fat accumulation, inflammation, and fibrosis. Meanwhile, the gut microbiota acts as a key regulator of host metabolism and immune function through the gut-liver axis, influencing bile acid metabolism, short-chain fatty acid production, and inflammatory signaling pathways. Diet is one of the main determinants of microbiota composition and function, and plant-based diets have been associated with increased microbial diversity and beneficial metabolic profiles.
Despite these advances, there is currently a lack of randomized clinical trials specifically evaluating the effects of a Mediterranean diet exclusively based on plant-derived foods in patients with MetLD, particularly considering the integrated assessment of hepatic outcomes, cardiometabolic risk factors, gut microbiota, genetic susceptibility, and environmental contaminant exposure.
This study is a randomized, controlled, parallel-group clinical trial designed to compare the effects of two dietary interventions: (1) a traditional Mediterranean diet, which includes both plant- and animal-based foods and is considered the standard of care in this setting, and (2) a Mediterranean diet exclusively based on plant-derived foods. Participants will be randomly allocated in a 1:1 ratio using a computer-generated randomization sequence with stratification by age and sex.
The intervention will last 12 weeks, followed by a 4-week post-intervention follow-up period aimed at evaluating adherence, sustainability, and integration of lifestyle changes. The study adopts a pragmatic design to enhance external validity, allowing participants to follow ad libitum dietary intake within structured dietary guidelines, guided by internal hunger and satiety cues rather than strict caloric prescriptions.
All participants will undergo a comprehensive baseline assessment, including clinical evaluation, dietary assessment, anthropometric measurements, blood pressure, and non-invasive liver evaluation using transient elastography with controlled attenuation parameter (CAP). Biological samples (blood, urine, feces, and hair) will be collected at baseline and at the end of the intervention to allow intra-individual comparisons.
Dietary interventions will be individually tailored by registered dietitians based on participants' clinical characteristics, preferences, and estimated energy requirements. Both dietary patterns will emphasize whole, minimally processed foods and adherence to Mediterranean dietary principles. The plant-based intervention group will exclude all animal-derived foods and will receive standardized vitamin B12 supplementation to prevent deficiencies.
Dietary intake will be monitored through repeated 24-hour dietary recalls conducted at multiple time points throughout the intervention, including both weekdays and weekends. Participants will also provide photographic records of meals to enhance data accuracy. Nutrient intake will be analyzed using specialized dietary analysis software. Continuous dietary counseling and support will be provided to promote adherence.
Comprehensive outcome assessments will include biochemical, metabolic, inflammatory, and functional parameters. Laboratory analyses will include liver enzymes, lipid profile, glucose metabolism markers, iron status, and systemic inflammatory markers such as C-reactive protein and the neutrophil-to-lymphocyte ratio.
Environmental exposure assessment will include quantification of PFAS in serum samples using high-performance liquid chromatography coupled with tandem mass spectrometry and isotopic dilution techniques. Heavy metals will be measured in hair samples using inductively coupled plasma mass spectrometry (ICP-MS/MS), providing an estimate of chronic exposure.
Gut microbiota composition will be analyzed using 16S rRNA gene sequencing, focusing on diversity indices, taxonomic composition, and functional profiles. Genetic analyses will be performed on blood samples to identify polymorphisms associated with MetLD susceptibility and progression.
Standardized and validated questionnaires will be used to assess physical activity, adherence to the Mediterranean diet, and quality of life. Additionally, body composition will be evaluated using bioelectrical impedance analysis, and muscle strength will be assessed using handgrip dynamometry.
The primary objective of the study is to evaluate the effect of a plant-based Mediterranean diet on liver health, assessed non-invasively through elastographic and biochemical parameters. Secondary objectives include the evaluation of changes in anthropometric and cardiometabolic parameters, systemic inflammation, gut microbiota composition, genetic modulation of dietary response, and internal exposure to environmental contaminants.
Data will be collected and managed using a secure electronic data capture system, ensuring data quality, confidentiality, and compliance with regulatory standards. Statistical analyses will be performed using appropriate descriptive and inferential methods, including multivariate regression models to account for potential confounders.
The study will be conducted in accordance with the principles of Good Clinical Practice and the Declaration of Helsinki. Ethical approval will be obtained from the relevant institutional review board, and all participants will provide written informed consent prior to inclusion.
This study is expected to provide novel, integrative evidence on the role of dietary patterns in modulating liver health, metabolic function, environmental exposures, and host-microbiome interactions. The findings may contribute to the development of more effective, sustainable, and personalized nutritional strategies for the prevention and management of MetLD, supporting the integration of precision nutrition and planetary health into clinical practice.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Traditional Mediterranean diet | Experimental | Other: Traditional Mediterranean dietThis dietary pattern is considered the standard of care in the study setting and includes a balanced intake of plant- and animal-derived foods, consistent with current clinical recommendations for metabolic liver disease. The diet emphasizes high consumption of vegetables, fruits, legumes, whole grains, nuts, seeds, and olive oil as the primary source of fat. Moderate intake of fish, poultry, eggs, and low-fat dairy products will be encouraged, while red and processed meats, added sugars, and ultra-processed foods will be limited. |
| Vegan Mediterranean diet | Experimental | Other: Vegan Mediterranean dietThis dietary pattern is designed and supervised by registered dietitians and emphasizes high consumption of vegetables, fruits, legumes, whole grains, nuts, seeds, and olive oil as the primary source of fat, in line with Mediterranean dietary principles. All animal-derived foods (including meat, fish, seafood, dairy products, and eggs) will be excluded. Legumes, whole grains, nuts, and seeds will serve as the main sources of protein and healthy fats. Participants will be encouraged to prioritize whole, minimally processed foods; however, plant-based alternatives to meat and dairy may be allowed in cases where necessary to support adherence. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Adults aged 18 to 75 years.
- Diagnosis of metabolic dysfunction-associated liver disease (MetLD) based on evidence of hepatic steatosis by ultrasound or transient elastography with controlled attenuation parameter (CAP) ≥ 275 dB/m, or liver biopsy.
- Body mass index (BMI) between 25 and 38.5 kg/m².
Key exclusion criteria (9 listed)
- Liver disease of etiology other than MetLD.
- Any condition requiring specific dietary treatment and/or limiting adherence to a plant-based diet.
- Acute or chronic diseases that may reduce life expectancy.
- Type 1 diabetes mellitus.
- Use of weight-loss medications (e.g., incretin-based therapies) or initiation of glucose-lowering medication within the past 6 months.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Traditional Mediterranean dietThis dietary pattern is considered the standard of care in the study setting and includes a balanced intake of plant- and animal-derived foods, consistent with current clinical recommendations for metabolic liver disease. The diet emphasizes high consumption of vegetables, fruits, legumes, whole grains, nuts, seeds, and olive oil as the primary source of fat. Moderate intake of fish, poultry, eggs, and low-fat dairy products will be encouraged, while red and processed meats, added sugars, and ultra-processed foods will be limited. | Other | Traditional Mediterranean diet |
| Vegan Mediterranean dietThis dietary pattern is designed and supervised by registered dietitians and emphasizes high consumption of vegetables, fruits, legumes, whole grains, nuts, seeds, and olive oil as the primary source of fat, in line with Mediterranean dietary principles. All animal-derived foods (including meat, fish, seafood, dairy products, and eggs) will be excluded. Legumes, whole grains, nuts, and seeds will serve as the main sources of protein and healthy fats. Participants will be encouraged to prioritize whole, minimally processed foods; however, plant-based alternatives to meat and dairy may be allowed in cases where necessary to support adherence. | Other | Vegan Mediterranean diet |
Primary outcome
Body weight
Time frame: Baseline and 12 weeks
Change from baseline to 12 weeks in body weight (kg), measured using bioelectrical impedance analysis under standardized conditions.
Hepatic steatosis
Time frame: Baseline and 12 weeks
Change from baseline to 12 weeks in hepatic steatosis measured non-invasively using transient elastography. Hepatic steatosis will be assessed by the controlled attenuation parameter (CAP, dB/m)
23 secondary outcomes
Liver stiffness
Time frame: Baseline and 12 weeks
Fat mass
Time frame: Baseline and 12 weeks
Waist circumference
Time frame: Baseline and 12 weeks
Systolic blood pressure
Time frame: Baseline and 12 weeks
Diastolic blood pressure
Time frame: Baseline and 12 weeks
Fasting glucose
Time frame: Baseline and 12 weeks
Fasting insulin
Time frame: Baseline and 12 weeks
Total cholesterol
Time frame: Baseline and 12 weeks
Low-density lipoprotein cholesterol
Time frame: Baseline and 12 weeks
High-density lipoprotein cholesterol
Time frame: Baseline and 12 weeks
Triglycerides
Time frame: Baseline and 12 weeks
Iron status
Time frame: Baseline and 12 weeks
Ferritin
Time frame: Baseline and 12 weeks
Transferrin saturation
Time frame: Baseline and 12 weeks
C-reactive protein
Time frame: Baseline and 12 weeks
Neutrophil-to-lymphocyte ratio
Time frame: Baseline and 12 weeks
Gut microbiota alpha diversity
Time frame: Baseline and 12 weeks
Gut microbiota taxonomic composition
Time frame: Baseline and 12 weeks
Serum PFAS concentrations
Time frame: Baseline and 12 weeks
Change in hair heavy metal concentrations (lead, cadmium, mercury, arsenic)
Time frame: Baseline and 12 weeks
Genetic variants
Time frame: Baseline
Health-related quality of life
Time frame: Baseline and 12 weeks
Liver disease-specific quality of life
Time frame: Baseline and 12 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Apr 2026.
- Background: PubMed 40222485Younossi ZM, Zelber-Sagi S, Lazarus JV, Wong VW, Yilmaz Y, Duseja A, Eguchi Y, Castera L, Pessoa MG, Oliveira CP, El-Kassas M, Tsochatzis E, Fan JG, Spearman CW, Tacke F, Castellanos Fernandez MI, Alkhouri N, Schattenberg JM, Romero-Gomez M, Noureddin M, Allen AM, Ong JP, Roberts SK, Shubrook JH, Burra P, Kohli R, Kautz A, Holleboom AG, Lam B, Isaacs S, Macedo P, Gastaldelli A, Henry L, Ivancovsky-Wajcman D, Nader F, de Avila L, Price JK, Mark HE, Villota-Rivas M, Barbera A, Kalligeros M, Gerber LH, Alqahtani SA. Global Consensus Recommendations for Metabolic Dysfunction-Associated Steatotic Liver Disease and Steatohepatitis. Gastroenterology. 2025 Oct;169(5):1017-1032.e2. doi: 10.1053/j.gastro.2025.02.044. Epub 2025 Apr 11.
- Background: PubMed 38851997European Association for the Study of the Liver (EASL); European Association for the Study of Diabetes (EASD); European Association for the Study of Obesity (EASO). EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). J Hepatol. 2024 Sep;81(3):492-542. doi: 10.1016/j.jhep.2024.04.031. Epub 2024 Jun 7.
- Background: PubMed 39982647Lopez-Moreno M, Kraselnik A. The Impact of Plant-Based Proteins on Muscle Mass and Strength Performance: A Comprehensive Review. Curr Nutr Rep. 2025 Feb 21;14(1):37. doi: 10.1007/s13668-025-00628-1.
- Background: PubMed 40138066Lopez-Moreno M, Fresan U. Do the Health Benefits of the Mediterranean Diet Increase with a Higher Proportion of Whole Plant-Based Foods? Curr Nutr Rep. 2025 Mar 26;14(1):52. doi: 10.1007/s13668-025-00647-y.
- Background: PubMed 41843153Lopez-Moreno M, Marrero-Fernandez P, Galiana C, Aguilar-Navarro M, Munoz A, Gutierrez-Hellin J, Fresan U. Environmental and economic impact of a vegan versus traditional mediterranean diet: OMNIVEG study. Eur J Nutr. 2026 Mar 17;65(3):97. doi: 10.1007/s00394-026-03939-3.
- Background: PubMed 39358106Lopez-Moreno M, Fresan U, Del Coso J, Aguilar-Navarro M, Iglesias Lopez MT, Pena-Fernandez J, Munoz A, Gutierrez-Hellin J. The OMNIVEG STUDY: Health outcomes of shifting from a traditional to a vegan Mediterranean diet in healthy men. A controlled crossover trial. Nutr Metab Cardiovasc Dis. 2024 Dec;34(12):2680-2689. doi: 10.1016/j.numecd.2024.08.008. Epub 2024 Aug 23.
- Individual participant dataSharing planned: No. Individual participant data (IPD) will not be shared.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Traditional Mediterranean diet and Vegan Mediterranean diet in people with Metabolic Dysfunction-associated Liver Disease, run by Miguel López Moreno at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 6 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Miguel López Moreno, PhD (+34 64892334, miguel.lopez@ufv.es), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Body weight (time frame: Baseline and 12 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07503431, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Apr 2026.